mRNA-Based Therapy for Pancreatic Cancer
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The pancreas is a glandular organ that lies behind the lower part of the stomach. Pancreatic cancer is a type of cancer arising from tissues in the pancreas. Pancreatic adenocarcinoma (PAAD) is the most common type of cancer (accounts for about 90%) that forms in the pancreas, which begins in the cells that line the ducts (the cells run out of control and become lumps). Therefore, the term "pancreatic cancer" is sometimes used to refer only to pancreatic adenocarcinoma. At present, the choice of treatment options for pancreatic cancer mainly depends on the extent of cancer, involving adjuvant chemotherapy, surgical resection, radiation therapy, or a combination of these. The treatment of pancreatic cancer remains a considerable challenge, due to its typically late presentation, resistance to chemotherapy, early metastasis, and other factors. And it is postoperatively recurrent in many patients.
Therapeutic vaccines for pancreatic cancer
Prototypical cancer vaccines are composed of a tumor antigen along with or without an adjuvant, which can reprogram the immune system to target and kill cancer cells. Cancer vaccines have many superior advantages, including minimal non-specific effects, relative non-toxicity, and induction of persistent immunological memory and so on. Compared with standard chemo- and immunotherapies, cancer vaccines have reduced adverse reactions, higher therapeutic efficacy as well as lower costs.
There are several types of vaccine strategies for pancreatic cancer, including,
- Dendritic cell-based vaccines.
- Peptide and protein vaccines.
- Whole cancer cell-based vaccines.
- Recombinant virus-based vaccines.
- Listeria-based vaccines.
mRNA-based therapy for pancreatic cancer
Cancer vaccines can be classified into several types according to the antigen form, including peptide, dendritic cell, tumor cell, DNA and RNA-based types. For the first four types, there are some disadvantages that limit their clinical potential. For instance, the development of DC vaccines is resource-consuming and time-consuming. DNA vaccines have the risk of insertional mutations. In contrast, mRNA-based vaccines have a good safety profile and can be rapidly, flexibly, and cost-effectively manufactured. Besides, mRNA sequences can be designed to encode any pathological antigen, which is highly significant for individualized therapies.
A recent study had firstly screened and identified potent antigens in PAAD for developing mRNA vaccine. A series of targetable antigens as promising mRNA vaccine candidates were identified, including ADAM9, TPX2, EFNB2, MET, TMOD3, and WNT7A. The study also constructed an immune landscape and demonstrated that patients with immune subtypes 4 and 5 were suitable candidates for vaccination. In addition, researchers are testing a mRNA-based vaccine that targets KRAS mutations in solid tumor cancers, including pancreatic cancer. The KRAS gene belongs to the RAS gene family, which plays an important role in regulating cell activity with respect to cell growth, survival, division, and death. The results of KRAS mutations lead to uncontrolled cellular growth and ultimately cancer. Since 95% of pancreatic cancers have KRAS mutations, considerable efforts have been made to find ways to target proteins and block their abnormal signaling activity.
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- Huang, X., et al. (2021). "Identification of tumor antigens and immune subtypes of pancreatic adenocarcinoma for mRNA vaccine development." Molecular cancer, 20(1), 1-18.
- Tekkesin, N., & Tetik, S. (2019). "Therapeutic vaccines for pancreatic cancer." Theranostic Approach for Pancreatic Cancer. Academic Press, 2019. 275-294.